This research project includes both the synthesis and biological evaluation of trimetoquinol derivatives with our prime goal being to develop potent and highly selective beta-adrenergic agents. The various derivatives of trimetoquinol, a potent beta-adrenergic stimulant, will be studied for their relative degree of adreno-receptor interaction. The quantitative interaction of these derivatives will be examined, the beta-adrenergic tissues, tracheobronchial muscle, cardiac tissue and adipose tissue. These compounds will also be tested in an isolated aorta preparation for the purpose of assessing gamma-adrenergic activity. We plan to study the mechanism of action of trimetoquinol and selected synthetic derivatives by elucidating their interaction with adenylate cyclase and cyclic-3',5'-adenosine monophosphate phosphodiesterase and correlating these effects with changes in tissue levels of cyclic-3',5'- adenosine monophosphate and the observed pharmacological response. These findings will provide valuable insight into the development of highly selective beta-adrenoreceptive agents. Bibliographic references: D.D. Miller, W.V.P. Merritt, P.F. Kador and D.R. Feller, Synthesis and Biological Actions of Fragmented Derivatives of Tetrahydroisoquinolines, J. Med. Chem., 18, 99 (1975); D.D. Miller, P. Osei-Gyimah, J. Bardin and D.R. Feller, Synthesis and Biological Actions of Fragmented Derivatives of Tetrahydroisoquinolines 2. Trimetoquinol Studies, J. Med. Chem., 18, 454 (1975).